OBJECTIVE To investigate the efficacy and safety of tirofiban for early neurological deterioration in patients with acute ischemic stroke. METHODS A total of 126 patients with early neurological deterioration of acute ischemic stroke who were admitted to the Department of Neurology， Heji Hospital Affiliated to Changzhi Medical College from January 2022 to December 2023 were selected and divided into observation group and control group according to random number table method， with 63 cases in each group. All patients received standardized treatment such as lipid-lowering and blood pressure-lowering therapy. Based on the standard treatment， patients in the control group additionally took Aspirin enteric-coated tablets 100 mg+Clopidogrel bisulfate tablets 75 mg orally （once a day， for 14 consecutive days）. The patients in the observation group received Tirofiban hydrochloride and sodium chloride injection based on the standardized treatment [first intravenous infusion of 0.40 μg/（kg·min） for 30 min， and then continuous intravenous infusion of 0.10 μg/（kg·min） for 47.5 h]； subsequently， patients were given Aspirin enteric-coated tablets （100 mg） and Clopidogrel bisulfate tablets （75 mg） once a day for 14 consecutive days. The clinical efficacy， the National Institutes of Health Stroke Scale （NIHSS） score， modified Rankin Scale （mRS） score， and hemorheological indexes before and after treatment were compared between the two groups， and the adverse reactions were recorded. RESULTS The total effective rate （87.30%） of the observation group was significantly higher than that of the control group （71.43%） （P＜0.05）. NIHSS scores of the two groups at 1st， 7th and 14th day after treatment， the mRS score at 90th day after treatment， and the platelet aggregation rate， whole blood viscosity， plasma viscosity and fibrinogen at 14th day after treatment were significantly lower than those before treatment in the same group， and the observation group was significantly lower than the control group at the same period （P＜0.05）. The total incidences of adverse reactions such as nausea， headache， fever， gastrointestinal bleeding， oral and nasal mucosal bleeding and thrombocytopenia in both groups of patients were 28.57% respectively， with no statistically significant difference （P＞0.05）. CONCLUSIONS For patients with early neurological deterioration in acute ischemic stroke， the addition of tirofiban can accelerate the recovery of neurological function， improve blood hyperviscosity and platelet aggregation， and improve the prognosis of patients with good safety.

Neuropathic pain is a debilitating pathological condition that presents significant therapeutic challenges in clinical practice. Unfortunately, current pharmacological treatments for neuropathic pain lack clinical efficacy and often lead to harmful adverse reactions. As G protein-coupled receptors (GPCRs) are widely distributed throughout the body, including the pain transmission pathway and descending inhibition pathway, the development of novel neuropathic pain treatments based on GPCRs allosteric modulation theory is gaining momentum. Extensive research has shown that allosteric modulators targeting GPCRs on the pain pathway can effectively alleviate symptoms of neuropathic pain while reducing or eliminating adverse effects. This review aims to provide a comprehensive summary of the progress made in GPCRs allosteric modulators in the treatment of neuropathic pain, and discuss the potential benefits and adverse factors of this treatment. We will also concentrate on the development of biased agonists of GPCRs, and based on important examples of biased agonist development in recent years, we will describe universal strategies for designing structure-based biased agonists. It is foreseeable that, with the continuous improvement of GPCRs allosteric modulation and biased agonist theory, effective GPCRs allosteric drugs will eventually be available for the treatment of neuropathic pain with acceptable safety.

ObjectiveBased on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway， this paper explores the effect of Sinisan （SNS） on liver oxidative stress injury in cholestatic hepatitis rats and its mechanism. MethodThirty 6-week-old male SD rats were randomly divided into a control group， model group， low and high dose groups of SNS （2.5 and 5 g·kg^-1） and ursodeoxycholic acid group （UDCA， 63 mg·kg^-1）， with six rats in each group. Rats were administrated for seven consecutive days. On the 5th day， the control group was given olive oil of 10 mL·kg^-1， and the other groups were given alpha-naphthalene isothiocyanate （ANIT） of 80 mg·kg^-1. The serum biochemical indicator levels of cholestasis and the content of antioxidant factors in rat liver were detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in liver tissue. The relative mRNA and protein expressions of Nrf2， HO-1， and quinone oxidoreductase 1 （NQO1） in liver tissue were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the control group， the model group showed a significant increase in the serum biochemical indicator levels of cholestasis and the content of antioxidant factors in liver tissue （P<0.01）. There were obvious pathological changes in the model group such as the disordered arrangement of hepatocytes， obvious congestion and necrosis in the portal area， infiltration of inflammatory cells， and destruction of the interlobular bile duct. The relative mRNA and protein expressions of Nrf2， HO-1， and NQO1 in liver tissue were significantly down-regulated in the model group （P<0.05， P<0.01）. Compared with the model group， the groups of SNS showed a significant decrease in the serum biochemical indicator levels of cholestasis and the content of antioxidant factors in liver tissue （P<0.01）， and the pathological liver injury was obviously improved. The necrotic area was reduced， and the infiltration of inflammatory cells was decreased. In addition， there was a small amount of extravasated blood in the interlobular vein. The relative mRNA and protein expressions of Nrf2， HO-1， and NQO1 in liver tissue were significantly up-regulated （P<0.05， P<0.01）. ConclusionSNS can significantly improve liver injury in cholestatic hepatitis rats， and its mechanism may be related to the inhibition of oxidative stress response mediated by the Nrf2/HO-1 signaling pathway.

In recent years， the incidence of pulmonary nodules has kept rising. To give full play to the advantages of traditional Chinese medicine （TCM） in the treatment of pulmonary nodules and identify the breakthrough points of integrating TCM with Western medicine， the China Association of Chinese Medicine organized medical experts in TCM and western medicine to carry out in-depth discussion regarding this disease. The discussion encompassed the modern medical advances， TCM theories of etiology and pathogenesis， the role and advantages of TCM in the whole course management of pulmonary nodules， contents and methods of research on pulmonary nodules， and science popularization work， aiming to provide a reference for clinical practice and scientific research. After discussion， the experts concluded that the occurrence of pulmonary nodules was rooted in the deficiency of the lung and spleen and triggered by phlegm dampness， blood stasis， and Qi stagnation. TCM can treat pulmonary nodules by controlling and reducing nodules， improving physical constitution， ameliorating multi-system nodular diseases， reducing anxiety and avoiding excessive diagnosis and treatment， and serving as an alternative for patients who are unwilling or unfit for surgical treatment. At present， the optimal diagnosis and treatment strategy for pulmonary nodules has not been formed， which needs to be further studied from multiple perspectives such as clinical epidemiology， biology， and evidence-based medicine. The primary task of current research is to find out the advantages， effective prescriptions， and target populations and determine the effective outcomes of TCM in the treatment of pulmonary nodules. At the same time， basic research should be carried out to explore the etiology and biological behaviors of pulmonary nodules. The expert consensus on the diagnosis and treatment of pulmonary nodules with integrated TCM and Western medicine needs to be continuously revised to guide clinicians to conduct standardized， scientific， and accurate effective diagnosis and treatment.

Objective To compare the diagnostic value of smear acid-fast staining,TB-DNA,X-pert MTB/RIF and culture of Mycobacterium tuberculosis.Methods Four methods were used to detect the perifocal pus of the patients with bone destruction in orthopaedics department within one year,and the results were analyzed statistically,the indexes included sensitivity,specificity,positive predictive value and negative predictive value.Results The sensitivity,specificity,positive predictive value,negative predictive value,and Youden index were 31.75%,100.00%,100.00%,53.74%and 0.32 respectively.TB-DNA had a sensitivity of 88.89%,a specificity of 98.00%,a positive predictive value of 98.25%,a negative predictive value of 87.50%,and a Youden Index of 0.87.Xpert MTB/Rif had a sensitivity of 95.23%,a specificity of 68.00%,and a positive predictive value of 78.95%,the negative predictive value was 91.90%,the Youden index was 0.63.The sensitivity,the specificity,the positive predictive value,the negative predictive value and the Youden index were 41.27%,100.00%,100.00%,57.47%and 0.41 respectively,(χ2 = 77.354,P<0.005).Conclusion Among the four methods,TB-DNA has a good Sensitivity and specificity,Xpert mtbrif has a good sensitivity,TB-DNA and Xpert mtbrif ha a good authenticity,and both positive and negative predictive values are high,it has good value in the diagnosis of bone tuberculosis.

Objective To explore the value of plaque-to-aorta CT value ratio(standardized CT value)in differentiating coronary lipid and fibrous plaques,and to preliminarily analyze the stability of the cutoff.Methods Patients who underwent coronary computed tomography angiography(CCTA)and intravascular ultrasound(IVUS)within 1 week were included.The plaque CT value was obtained by measuring the all,four and two short-axis planes,respectively.The CT value of the ascending aorta was measured and standardized(plaque-to-aorta CT value ratio).The receiver operating characteristic(ROC)curves of the standardized and the traditional CT values were drawn.Results A total of 60 patients with 74 plaques were included,35 lipid and 39 fibrous plaques were diagnosed by IVUS.The aorta CT value was significantly correlated with the plaque(r=0.420,P<0.01);the cutoffs for the CT value of all,four and two plaque slices were 55 HU,48 HU and 52 HU,respectively,and all there of the cutoffs of standardized CT value were 0.149;the sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV)of four-slice traditional and standardized CT values to differentiate lipid and fibrous plaques were 69%,87%,83%,76%and 91%,82%,82%,91%,respectively.Conclusion Compared with traditional CT value,the standardized CT value can greatly improve the sensitivity and NPV in differentiating coronary lipid and fibrous plaques,while maintaining modest to high specificity and PPV.Furthermore,the cutoff is stable.

Objective:To investigate the regulatory effect of transient receptor potential cation channel subfamily C member 3 (TRPC3) on the retina in oxygen-induced retinopathy (OIR) mice and biological behavior of human retinal vascular endothelial cells (HREC).Methods:A total of 32 healthy SPF grade 7-day-old C57BL/6 mice were selected and randomly divided into a control group and an OIR group by the random number table method, with 16 mice in each group.The control group received no special treatment, and the OIR model was established in the OIR group.On postnatal day 17 (PN17), the success of the model establishment was verified by immunofluorescence staining of the retinal patch.The in vitro cultured HREC were divided into a normal control group, a transfection reagent group, and a si-TRPC3 group.The normal control group received no special treatment, while the transfection reagent group and the si-TRPC3 group were transfected with transfection reagent or transfection reagent + si-TRPC3.The relative expression of TRPC3 mRNA was detected by real-time quantitative fluorescence PCR.The relative expressions of TRPC3, transcription factor NF-E2 related factor (Nrf2), and superoxide dismutase (SOD) proteins were determined by Western blot.HREC were further divided into a normal control group, a vascular endothelial growth factor (VEGF) group, a si-TRPC3 group, and a Pyr3 (TRPC3 channel inhibitor) group, which were cultured in complete medium, medium containing 20 ng/ml VEGF recombinant protein, medium containing 20 ng/ml VEGF recombinant protein (si-TRPC3 transfection for 72 hours), and medium containing 20 ng/ml VEGF recombinant protein+ 1 μmol/L Pyr3 for 48 hours, respectively.The proliferation ability of HREC was detected using cell counting kit 8 (CCK-8). The horizontal and vertical migration ability of cells were detected by cell scratch assay and transwell assay, respectively.This study followed the 3R principles of animal welfare and was approved by the Ethics Committee of Hebei Eye Hospital (No.2023LW04). Results:Pathological neovascular clusters with strong fluorescent staining appeared in the retina of OIR mice on PN17.The relative expressions of TRPC3 mRNA and protein in the retina of OIR mice were 2.057±0.244 and 1.517±0.290, respectively, significantly higher than 0.983±0.033 and 0.874±0.052 of control group ( t=6.165, 3.094; both at P<0.05). The relative expression levels of TRPC3 mRNA and protein were significantly lower, and the relative expression levels of Nrf2 and SOD proteins were higher in the si-TRPC3 group than in the normal control and transfection reagent groups, and the differences were statistically significant (all at P<0.05). The CCK-8 experiment results showed that the cell absorbance value was higher in the VEGF group than in the normal control group, and lower in the si-TRPC3 and Pyr3 groups than in the VEGF group, with statistically significant differences (all at P<0.05). The results of the cell scratch experiment showed that the lateral migration rate of VEGF group cells was higher than that of normal control group, while the lateral migration rate of si-TRPC3 group and Pyr3 group cells was lower than that of VEGF group, and the differences were statistically significant (all at P<0.05). The transwell experiment results showed that the number of stained cells in the VEGF group was higher than that in the normal control group, and the number of stained cells in the si-TRPC3 group and Pyr3 group was lower than that in the VEGF group, with statistically significant differences (all at P<0.05). Conclusions:Hypoxia induces increased TRPC3 expression in OIR mouse retina, and downregulation of TRPC3 inhibits HREC proliferation and migration.The mechanism is related to the activation of the Nrf2-related oxidative stress pathway.

Objective:To investigate the current situation of satisfaction with graduate education among recent medical graduates in China, and analyze the differences between different populations, and to propose countermeasures and suggestions.Methods:From June to July 2023, a self-made questionnaire was used to survey 16 903 medical graduates who had recently earned a post-graduate degree from 78 institutions about their satisfaction with curriculum sessions, practical sessions, research training, tutoring, and institutional management. The degrees of satisfaction with education among different populations were compared through the t test and analysis of variance with the use of SPSS 26.0. Results:The scores of satisfaction of the graduates with tutoring, curriculum sessions, practical sessions, institutional management, and research training were 4.44, 4.03, 4.02, 3.90, and 3.82, respectively. Satisfaction scores for individual dimensions were significantly higher for males, doctors, non-transfers, comprehensive universities, non-agricultural household registration, moderate-to-high annual household income per capita, parents with high educational levels, and parents with mid- or senior-level occupations ( P<0.05). Conclusions:There is room for improvement in students' satisfaction with medical graduate education. To improve the quality of medical graduate education, attention should be paid to key populations, education policies, school management, and tutoring to provide appropriate education for different students.

Objective To systematically evaluate the efficacy of partial splenic artery embolization(PSE)and splenectomy in the treatment of secondary hypersplenism in liver cirrhosis.Methods PubMed,Cochrane Library,Embase,CNKI,Wan Fang were searched to collect randomized controlled trials and cohort studies about the efficacy of PSE versus splenectomy in the treatment of hyper-splenism secondary to liver cirrhosis from inception to October 30,2021.Two reviewers screened the literature,extracted data,and as-sessed the risk of bias of included studies.Meta-analysis was then conducted.Results A total of 14studies were included with 1092 patients.The results of the meta-analysis showed that there was no significant difference in postoperative leukocyte levels at 1 week,1 month,and 1 year after surgery between the PSE group and the splenectomy group.However,6months after surgery,the level of postop-erative leukocyte in the splenectomy group was significantly higher than that in the PSE group.For postoperative platelet counts,there was no significant difference at 1 month and 1 year after surgery between the two groups.However,1 week(MD=-65.46,95％CI:-116.39--14.52,P=0.01)and 6months(MD=-117.99,95％CI:-229.71--6.27,P=0.04)after surgery,the level of postoperative platelet in splenectomy group was significantly higher than that in PSE group.There was no significant difference in postoperative erythro-cyte levels at 1 week,1 month,and 1 year after surgery between the two groups.The level of postoperative natural killer cells in the PSE group was significantly higher than that in the splenectomy group at 1 month(MD=6.02,95％CI:4.27-7.77,P＜0.001)and 1 year(MD=3.53,95％CI:1.68-5.37,P=0.0002)after surgery.Compared with splenectomy group,PSE group exhibited less intraopera-tive bleeding(MD=-73.92,95％CI:-89.39--58.45,P＜0.001),less hospitalization costs(MD=-0.80,95％CI:-1.27--0.34,P=0.0008)and shorter length of stay(MD=-4.08,95％CI:-5.22--2.95,P＜0.001).Conclusion The current evi-dence shows that PSE has certain short-term and long-term effects on hypersplenism.Compared with splenectomy,it has less surgical trauma,less hospital stay and less cost,easy to control complications,and retains some immune function,which is worth spreading in the clinic.Limited by the quantity and quality of the included literature,more high-quality studies are needed to confirm the above conclu-sions.

Objective To evaluate the efficacy and safety of tigecycline combined with cefoperazone-sulbactam sodium in the treatment of multi-/extensively-drug resistant Acinetobacter baumannii(MDRAB/XDRAB)associated central nervous system(CNS)infection,and to provide clinical evidence for antibiotic treatment of MDRAB/XDRAB-related intracranial disease.Methods The Wanfang Data Knowledge Service Platform,Chinese Biomedical Literature Database,VIP Chinese Science and Technology Journal Full-text Database,China National Knowledge Infrastructure(CNKI),Pubmed,Embase database,and Cochrane Library were searched to extract the literature of randomized controlled studies on tigecycline and cefoperazone sulbactam in the treatment of MDRAB/XDRAB CNS infection until September 1st,2022.The included studies were assessed for quality using the Cochrane Collaboration Risk of Bias assessment tool,and valid data were extracted and meta-analyzed using RevMan5.4 software.Results A total of 184 articles were screened and 4 Chinese RCTs were finally included,with a sample size of 267 cases.Meta-analysis showed that the overall efficacy of combination therapy for MDRAB/XDRAB CNS infection was better than monotherapy[OR = 4.30,95%CI =(1.93,9.58),P＜0.01].Combination therapy had a better bacterial clearance[OR=4.20,95%CI=(2.08,8.48),P＜0.01].And combination therapy resulted in a lower incidence of adverse effects[OR= 0.19,95%CI =(0.05,0.67),P＜0.05].There was no apparent difference in cure rate between combination therapy and monotherapy(P＞0.05).Conclusion Current evidence suggests that tigecycline combined with cefoperazone-sulbactam sodium may have better clinical efficacy and safety than monotherapy for MDRAB/XDRAB CNS infections.Limited by the number and quality of included studies,needs to be verified by more and higher-quality studies.